This application proposes experiments to examine the relationship between cell-to-cell communication of cAMP and the control of oocyte development. Previous studies have suggested that cAMP is transmitted from the cells of the cumulus oophorus to the oocyte and is responsible for maintaining meiotic arrest prior to ovulation. In this context, the termination of cumulus-oocyte communication, which occurs near the time of ovulation, would interrupt the supply of cAMP to the oocyte and allow meiosis and further development to ensue. The studies for which support is requested are designed to evaluate this hypothesis and to further examine the roles of communication and cAMP in the control of this naturally occurring heterologous cell system. Specifically we propose to correlate intracellular cAMP levels with the stage of oocyte development, to determine whether oocytes synthesize cAMP and to provide a direct demonstration of the transmission of cAMP from the cumulus cells to the oocyte. We will also examine the effect of CA++ and inhibitors of calmodulin on the communication of cAMP and oocyte development. The issue of the cAMP dependence of the phosphorylation of oocyte proteins and their relationship to oocyte maturation will be explored as will the potential involvement of plasminogen activator, which is produced by the cumulus, in the breakdown of cumulus-oocyte communication. Finally, the possibility that the cumulus cells communicate with other follicular cells will also be examined. These studies will be conducted using established methods and have as their long term goals (a) an understanding of the control of one cell by another as the result of communication, and (b) an understanding of the control of oocyte development. Although these investigations have clear implications for the study of reproductive biology, the issue being investigated has greater potential ramifications for the study of cell biology in general since this represents the first cellular system in which one cell type appears to control another, by the direct transfer of a substance between them, to synchronize the function of a physiological unit.